Figure 1.
Cartoon representation of the canonical MAPK signaling pathway.
Table 1.
State Variables of the MAPK cascade.
Table 2.
Parameter listing for model (1).
Figure 2.
Cartoon representation of the yeast scaffold-MAPK signaling complex.
Figure 3.
Schematic of activation and deactivation processes in the yeast scaffold-MAPK signaling complex.
Names are as given in table 3, with the star representing phosphorylated (and thus active) Fus3. Horizontal arrows represent phosphorylation/dephosphorylation events (P to D and vice versa and inactive Fus3 to active Fus3 and vice versa), while transitions from the inner layer to the membrane layer are binding reactions ( and
).
Table 3.
State variables for model 2.
Table 4.
Parameter listing for model (2).
Figure 4.
Dependence of the Hill coefficient on Michaelis-Menton binding constants in the canonical MAPK pathway.
(left) Spread of Hill coefficients calculated from model (1). Exponents for binding and kinetic constants for MAPK and MAPKK were drawn from a uniform (−3,3) distribution. (right) Representative Hill plots for model (1). Kinetic constants are . Lines represent
(diamonds),
(squares), and
(circles).
Figure 5.
Distribution of Hill coefficients of model 2 given binding constants (,
) with uniform log distributions.
Figure 6.
Signal response of the scaffold-MAPK complex in the presence () or absence (
) of constitutive
binding.
Plots represent slow (, left panel) or fast (
, right panel) scaffold-membrane association rates.
Figure 7.
Signal response of the scaffold-MAPK complex as a function of scaffold-membrane binding and alignment rate.
(left) Representative Hill plots for (dashed) and
(solid). (right) Dependence of the Hill coefficient on
. All other parameters as in table 4.
Figure 8.
Dependence of ultrasensitive output response on cytosolic phosphorylation of scaffolds.
Plots of Hill coefficient as a function of are shown for cytosolic rate control parameter
= 0 (circles), 0.1 (squares) and 1 (diamonds).
Figure 9.
Schematic representation of signal transduction with constitutive MAPKKK activity in the absence (left) and presence (right) of scaffold.
Figure 10.
Schematic representation of yeast pheromone signal transduction with proper (left) and abrogated (right) Fus3-Ste5 interaction.
Figure 11.
Abrogation of Fus3-scaffold interaction can lead to loss of ultrasensitive Fus3 response.
Wild-type (solid, , total activated scaffold) and Fus3-less (dashed,
, free active Fus3) scaffold system responses are plotted for
.